Dioxin-like (DL-) polychlorinated biphenyls induced immunotoxicity through apoptosis in mice splenocytes via the AhR mediated mitochondria dependent signaling pathways

• Published in: Food and chemical toxicology 2019-12, Vol.134, p.110803, Article 110803
• Main Authors: Du, Fang, Zhao, Ting, Ji, Hong-Chen, Luo, Ying-Biao, Wang, Fen, Mao, Guang-Hua, Feng, Wei-Wei, Chen, Yao, Wu, Xiang-Yang, Yang, Liu-Qing
• Format: Article
• Language: English
• Subjects: AhR; Animals; Apoptosis; Apoptosis - drug effects; Body Weight - drug effects; Cytokines; Cytokines - genetics; Cytokines - metabolism; Dioxins - toxicity; Female; Immunotoxicity; Male; Malondialdehyde - metabolism; Mice; Mice, Inbred ICR; Mitochondria - metabolism; Oxidative damage; Polychlorinated biphenyl; Polychlorinated Biphenyls - toxicity; Reactive Oxygen Species - metabolism; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - metabolism; RNA, Messenger - genetics; Signal Transduction; Spleen - cytology; Spleen - drug effects; Spleen - enzymology; Spleen - immunology; Superoxide Dismutase-1 - metabolism; Thymus Gland - drug effects; Thymus Gland - enzymology; Thymus Gland - metabolism
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2019.110803

Polychlorinated biphenyls (PCBs) would do serious damage to multiple systems, while coplanar polychlorinated biphenyls, the most toxic member of the family, has been widely taken into consideration. In this study, ICR mice were fed with different doses of PCB126 to explore the underlying molecular mechanisms on immunotoxicity. The results showed that PCB126 caused immunosuppression as evidenced by inhibiting the ratios of thymus and spleen weights, changing the organizational structure and decreasing levels and mRNA expression of TNF-α, IFN-γ and IL-2. PCB126 inhibited the SOD activity and spurred the accumulation of MDA in spleen and thymus. Meanwhile, it also disturbed the Nrf2 signaling pathway as evidenced by up-regulating the mRNA expression of Nrf2 and Keap1. Additionally, a remarkable reduction in the mRNA expression of AhR and enhancement in the mRNA expression of Cyp1 enzymes (Cyp1a1, Cyp1a2 and Cyp1b1) were observed, which increased the ROS levels. PCB126 could increase protein expression of Bax, Caspase-3, Caspase-8 and Caspase-9, while the protein expression of Bcl-2 was decreased. In summary, the results indicated that PCB126 modulated the AhR signaling pathway, which interacted with apoptosis and oxidative stress to induce immunotoxicity, enrich the immunotoxicological mechanisms of PCB126. [Display omitted] •PCB126 can stimulate ROS production via up-regulating mRNA expression of Cyp1.•PCB126 can impair the redox homeostasis via disturbing Nrf2-Keap1 pathway.•PCB126 can induce immunotoxicity.•PCB126 induce apoptosis via the intrinsic and extrinsic apoptosis pathway.